Accumulating data suggest that due to their influence on the topological state of the DNA, topoisomerases I and II (topo I, II) may control various biological processes. Because of their involvement in the control of such fundamental biological activities, it is tempting to speculate that the deranged expression of these enzymes may play an important role in neoplastic transformation. Therefore, in order to elucidate this possibility, we have searched for the possible in vivo interrelationships between these enzymes and activated oncogenes. The enzymatic activities of the topo II in oncogene-transfected cells differed from those observed in untransfected cells, mainly on the degree of dependence on adenosine triphosphate (ATP), spermidine and Mg+2. Normal rat kidney (NRK) cells infected with a temperature-sensitive mutant (ts110) of Moloney murine sarcoma virus (Mo-MuSV) had a very slight topo I activity at the permissive temperature (34 degree), while at the non-permissive temperature (39 degree) they exhibit a normal topo I activity. These cells produced p85 gag-mos proteins at 34 degree C, but not at 39 degree C. Moreover, these cells were resistant to topo I inhibitor effects at 34 degree C, but were sensitive at 39 degree C. Further experiments are needed to determine whether this absence inhibition of topo I activity is a direct effect of the p85 gag-mos protein.